Endometriosis is a common gynecological condition that affects 6-10% of women in the general population. It affects 38-50% of infertile women and 71-87% of women with chronic pelvic pain. The disorder is usually initially detected during the teenage years and peaks around the age of 40.
Endometriosis occurs when the cells that normally line the uterus (endometrium) enter the pelvis or bloodstream and attach to other organs. Endometrial cells have discovered in areas as distant as the lungs and brain, although they most commonly occur in the pelvic area. These endometrial implants can grow and damage the structures they are attached to, leading to organ dysfunction. Endometriosis is typically found on the fallopian tubes and can penetrate and obstruct these delicate structures.
Endometrial implants consist of the following cell types:
- Endometrial gland cells: cells that are normally located in the uterine lining
- Stromal cells: framework cells that build supportive tissue
Endometrial cells, which have receptors for both estrogen and progesterone, become implanted in organs and structures outside of the uterus. Responding to hormonal changes during the menstrual cycle, endometriosis patches bleed, causing pain and tissue scarring. These patches can be located in the peritoneum, ovaries, around the fallopian tubes, in the gastrointestinal tract (12-37%), around the bladder (20%), and (less commonly) in the vagina.
Areas affected by endometriosis vary widely in size, shape, and color. They may be colorless, red, or very dark brown. The so-called chocolate cysts, or endometriomas, are filled with thick, old, dark brown blood and are located inside the ovaries.
Many theories about the cause of endometriosis center around the possibility that this disorder represents a state of an impaired immune system, which allows the endometrial implants to invade and proliferate the body. Biopsies of endometriosis contain high levels of macrophages, which contain cytokines and prostaglandins. These factors produce inflammation and damage the surrounding tissues.
- FAMILY HISTORY – Women who have a mother or sister with endometriosis are ten times more likely to have the disease, indicating a likely genetic link.
Defined by the presence of endometrial glands and stroma outside the uterus. The most popular theory is retrograde menstruation with an altered immune response.
- Incidence is 6-10% in general population
- Begins in teenage years and peeks at age 40
Endometriosis disease sites
|Endometriosis Common Sites||Rare Sites|
|Pelvic peritoneum||Episiotomy scar|
|Ligaments of the uterus||Bladder|
|Pelvic lymph nodes||Arms|
|Fallopian tubes||Spinal column|
- Irritable bowel syndrome
- Interstitial cystitis
- Chronic fatigue
- Migraine headaches
Endometriosis pain and associated symptoms
- Chronic pain
- Pelvic visceral or muscle pain (abdominal, back, lower leg)
Blood vessels in the lesions of endometriosis are innervated by sensory and sympathetic supply (pain and sensory amplification) and thought to be the cause of pain.
Risk of endometriosis
Increased risk of endometriosis is associated with:
- Menses lasting longer than 6 days
- Heavy bleeding during menses
- Congenital uterine abnormalities, such as bicornate uterus or uterus didelphys
- Certain chemicals, such as dioxin, polychlorinated biphenyls (PCBs), and bisphenol A
Decreased risk of endometriosis is associated with:
- Increased parity (having more children)
- Irregular menses
- Oral contraceptive use
- Late menarche
|Androgens||Danazol||100 mg daily|
|Estrogen/progesterone||Monophasic OCP||Low ethinyl estradiol continuously|
|GnRH agonist||Goserelin||3.6 mg SC monthly|
|Lupron Depot||3.75 IM monthly|
|Nafarelin||200 mcg IM Bid|
|Progestin||Medroxy prog||30 po daily for 6 months|
|Norethindrone||5 mg daily|
Continuous oral contraceptive use (24 months) has been shown to decrease endometrioma recurrence from 29% to 8%.
Levonorgesterel IUD (6-12 months) can lead to secondary amenorrhea, which will decrease recurrence of symptoms, decrease pain, and is equivalent to GnRH agonist. The IUD has been effective in rectovaginal endometriosis.
GnRH agonist is often used together with northindrone acetate daily in order to decrease the effects on bone density as compared with GnRH agonist alone.
Cabergoline is an antiangiogenic with properties that may improve endometriosis (endometriotic lesions have dopamine receptor type-2 DRD2).
Simvastatin is an antiangiogenic agent shown to have inhibitory effect on endometriosis implants in mice.
Oral contraceptives combined with 2.5 mg daily of an aromatase inhibitor letrozole may also decrease pelvic pain symptoms after an individual has surgery.
Endometriosis infertility treatment
Patients with endometriosis may experience:
- Longer follicular phase (problem with LH surge)
- Luteal phase defects with lower progesterone
- Fewer follicles (eggs) in the ovary with substantial decrease in ovarian reserve after multiple surgeries
- Decreased oocyte quality
- Decreased ovulation
- Increased luteinized un-ruptured follicle syndrome
- Problems with fertilization
- Poor sperm binding and motility
The peritoneal fluid of women with endometriosis may contain elements like Interlukins (IL-6), which reduces sperm motility. Women with endometriosis have increased peritoneal macrophages, which can destroy sperm.
Endometriosis is associated with poor embryo quality and arrest of embryo development. GNRH agonist may improve embryo quality.
Endometriosis is associated with decreased implantation due to decreased integrins expression αVβ3, which can lead to reduced uterine receptivity.
Endometriosis is associated with increased spontaneous abortions up to 33%.
In vitro fertilization (IVF)
IVF is the most effective treatment for women with advanced stage endometriosis (Stage III and Stage IV). GnRh agonist treatment prior to IVF has been shown to improve IVF success rate.
Natural transfer, when the embryos are frozen and subsequently transferred in another cycle, is beneficial in increasing the pregnancy rates with IVF. This could be explained by the fact that high estrogen levels during an IVF cycle can have inhibitory effects on progesterone. This effect is eliminated if the embryos are transferred in another cycle.
At Advanced Fertility Center of Texas, we believe that many patients with endometriosis benefit from IVF with a Natural transfer (postponed embryo transfer).
Surgery (usually with laparoscopy) may benefit deeply infiltrating endometriosis in women who experience pelvic pain, painful menstruation, and painful intercourse. Pain after surgery occurs more often in women with mild endometriosis, as they are typically more sensitive to pain.
Some endometriosis lesions are more painful than others, but the reasons for this difference are not well understood.
One explanation is that there are some blood vessels in the lesions that are innervated by nerves that are both sensory and sympathetic (pain and sensory amplification).
Recurrence of pain after surgery
Over time, pain may be reactivated by hormonal changes due to progesterone resistance and increased aromatase activity. These factors increase inflammation in the lesions. Also, depression and anxiety can contribute to pain in some patients. Pain recurrence could also be due to incomplete removal of a lesion, either due to its location or a lack of recognition.
Endometrioma is described as a blood-containing pseudocyst resulting from ovarian endometriosis with hemorrhage. Medical therapy unfortunately will not cause regression of the endometrioma.
Most patients with an endometrioma are symptomatic and need to exclude malignancy.
Studies have demonstrated that the excision (surgery) of the endometrioma cyst is associated with a reduced rate of recurrence and increased spontaneous pregnancy when compared with ablation therapy. The recurrence rate of endometrioma after surgery is 8-29%. Continuous oral contraceptive use is beneficial post-surgery.
However, surgery for endometrioma can result in decreased ovarian reserve due to damage to the ovary and a decrease in the number of oocytes.
Endometrioma may not require surgery if it is measuring less than 5 centimeters and the patient is planning to have IVF.